Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54124, Macedonia, Greece.
Eur J Med Chem. 2011 Jan;46(1):297-306. doi: 10.1016/j.ejmech.2010.11.018. Epub 2010 Nov 19.
The synthesis of a number of benzimidazole Schiff bases 3 and 3-oxo-pyrimido[1,2-a]benzimidazoles 4 in excellent yields by a one-step sequence from the reaction of 2-aminobenzimidazole under green chemistry conditions is described. Structural assignments of the new compounds as well as complete assignment of (1)H and (13)C NMR signals have been unambiguously achieved based on the analysis of their (1)H and (13)C NMR (1D and 2D), IR, MS and elemental analysis data. To the synthesized Schiff bases the E-configuration was assigned on the basis of comparison of experimental and calculated (DFT) (13)C NMR chemical shifts. Compounds 3 and 4 were evaluated as inhibitors of lipoxygenase (LOX) and of lipid peroxidation (LPO). All the tested derivatives showed inhibition of lipid peroxidation, whereas most of them were found to have higher activation than the reference compound trolox; The Schiff bases 3e, 3h, and 3i, and the pyrimidobenzimidazoles 4a, 4e and 4f were found to be the most potent. The most potent LOX inhibitor within the subset of Schiff bases was found compound 3i, followed by 3f, whereas compounds 4a and 4g were found the most potent of the 3-oxo-pyrimido[1,2-a]benzimidazole group. Moreover, some cytotoxicity assessments were undertaken, whereupon it was found that Schiff base 3i and pyrimidobenzimidazoles 4e and 4f did not exhibit cytotoxicity at similar concentrations resembling thus the inhibitory activity of lipid peroxidation. The most cytotoxic Schiff base and pyrimidobenzimidazole were found to be 3d and 4c, respectively.
描述了在绿色化学条件下，通过 2-氨基苯并咪唑的一步反应，以优异的产率合成了一系列苯并咪唑席夫碱 3 和 3-氧代嘧啶并[1,2-a]苯并咪唑 4。根据对其 1H 和 13C NMR（一维和二维）、IR、MS 和元素分析数据的分析，明确了新化合物的结构分配以及（13）C NMR 信号的完整分配。基于实验和计算（DFT）（13）C NMR 化学位移的比较，将 E-构型分配给合成的席夫碱。化合物 3 和 4 被评估为脂氧合酶（LOX）和脂质过氧化（LPO）的抑制剂。所有测试的衍生物均显示出抑制脂质过氧化的作用，而其中大多数比参考化合物 trolox 具有更高的活性；席夫碱 3e、3h 和 3i 以及嘧啶苯并咪唑 4a、4e 和 4f 被发现具有最强的活性。在席夫碱亚组中，最强的 LOX 抑制剂是化合物 3i，其次是 3f，而化合物 4a 和 4g 是 3-氧代嘧啶并[1,2-a]苯并咪唑组中最强的。此外，还进行了一些细胞毒性评估，发现席夫碱 3i 和嘧啶苯并咪唑 4e 和 4f 在相似浓度下没有表现出细胞毒性，因此类似于脂质过氧化抑制活性。最具细胞毒性的席夫碱和嘧啶苯并咪唑分别为 3d 和 4c。
